Non-steroidal anti-inflammatory drugs (hereinafter referred to as "NSAID(S)") and acetaminophen (hereinafter referred to as "APAP") are known to be effective analgesics for the treatment of mild to moderate pain. Histamine receptor blockers (referred to generically herein as H.sub.1 or H.sub.2 blockers) are effective inhibitors of gastric acid production. Proton pump inhibitors have been recently introduced as effective gastric acid inhibitors.
The symptoms of overindulgence due to excessive or inappropriate intake of food and/or alcoholic beverage are well known and include headache as well as indigestion, upper abdominal discomfort, bloating, heartburn or pyrosis. These latter symptoms collectively are sometimes referred to as acid indigestion or sour stomach. Indigestion has been variously described and will be defined herein as encompassing one or more of the following symptoms: abdominal pain and/or pressure, heartburn, a sense of abdominal fullness or bloating, excessive belching or flatulence and a vague feeling that digestion has not proceeded naturally (See Friedman, L. S., and K. J. Isselbacher, "Indigestion", Harrison's Principles of Internal Medicine, 11th Edition, McGraw Hill Book Company, N.Y., p 171-175, 1986).
The pathophysiology of indigestion is generally believed to be related to increased intraluminal acidity. The effects of alcohol and/or food on the gastrointestinal tract are influenced by a number of factors, including the mental state of the patient, the amount and type of food concurrently ingested, the individual subject's tolerance for alcohol and the presence or absence of disease. Gastric secretions stimulated by alcohol are rich in acid and normal in pepsin content. Stimulation of the antral mucosa by alcohol also leads to increased gastric secretion. Histamine has also been shown to be released in response to the alcohol-gastrin inter-relationship. (See Glass, G. B. J., B. L. Slomiany and A. Slomiany, "Biochemical and Pathological Derangements of the Gastrointestinal Tract following Acute and Chronic Ingestion of Ethanol", Biochemistry and Pharmacology of Ethanol. Vol 1, Plenum Press, N.Y., p 551-586, 1979.)
Alcohol in concentrations of about 10% in the stomach results in an acid rich secretion. Alcoholic drinks of 40% concentration and over are quite irritating to the gastric mucosa and cause congestive hyperemia and inflammation of the gastric mucosa and can produce erosive gastritis (See Ritchie, J. M., "The Aliphatic Alcohols", The Pharmacological Basis of Therapeutics, 7th Edition, MacMillan Publishing Co, N.Y., p 372-386, 1985). The irritation produced by alcohol stimulates sensitized visceral afferent nerves which accompany the abdominal sympathetic pathway and is responsible for the symptom of abdominal discomfort which accompanies overindulgence. Inflammation also generally lowers the threshold for pain from visceral distention or exaggerated muscular contraction (See Lorber, S. H., and V. P. Dimoso, Jr., "Diseases of the Gastrointestinal Tract", The Biology of Alcoholism, Vol 3, Clinical Pathology, Plenum Press, N.Y., p 339-357, 1974).
Heartburn or pyrosis is frequently associated with overindulgence and is the result of reflux of acidic gastric content into the lower esophagus after a large meal or excessive alcohol intake. Heartburn is described as a sensation of warmth or burning located substernally or high in the epigastrum with occasional radiation into the neck and occasionally to the arms.
Treatment of the gastric mucosal irritation and heartburn associated with overindulgence due to alcohol has traditionally been directed toward reducing gastric acidity with various oral antacids. Recent introduction of H.sub.2 receptor blocking agents has added another dimension to the treatment regimen and has only lately been considered as a routine therapy for gastric mucosal irritation due to a variety of causes. Histamine is known to stimulate the release of gastric acid. Evidence is available that blocking the histamine gastric response is possible with agents which selectively block the H.sub.1 receptor. Similarly, combinations of H.sub. and H.sub.2 receptor blocking agents have been shown to have a synergistic effect on protecting the gastric mucosa. An appropriate treatment of heartburn or pyrosis could encompass a composition containing an H.sub. receptor blocking agent, an H.sub.2 receptor blocking agent or a combination of the two depending upon the desired result or severity of the condition.
Headache due to excessive food or alcohol ingestion is a much more obscure subject. While the etiology of the common headache due to overindulgence may be related to the essential oils, metabolic by-products of ethyl alcohol metabolism or osmotic changes induced by the anhydrous nature of the alcohol itself, specific details of the mechanism are difficult to determine. Should etiologies and mechanisms of headache production be more precisely known, therapy can be more specifically oriented. Meanwhile, treatment has been directed at avoidance and symptomatic therapy with analgesic compositions, e.g. aspirin or APAP (See Adams, R. D. and J. B. Martin, "Headache", Harrison's Principles of Internal Medicine, 11th Edition, McGraw Hill Book Company, N.Y., p 26-33, 1986).
The treatment of the symptoms of overindulgence often requires the co-administration of an analgesic to relieve the headache along with an agent to reduce gastric acidity which is generally believed to cause the indigestion and heartburn. For example, effervescent products comprising aspirin or APAP combined with an antacid such as sodium or calcium carbonates have been commercially available as treatments for the symptoms of overindulgence.
The concept of combining an agent to reduce or inhibit the production of gastric acid with an analgesic in a single composition has, however, heretofore been overlooked as a method of treating overindulgence. Such a combination would be a significant advance and meet a long felt need for treating the symptoms of overindulgence, permitting a single composition to more effectively treat all the symptoms concurrently.